Project Summary Most allergic reactions are caused by immunoglobulin E (IgE) antibodies that are specific for allergens and that trigger potent inflammatory responses mediated by mast cells and basophils. IgE binds to the high affinity receptor (Fc?RI) expressed on these allergic effector cells, making this a central interaction that is common to different allergen-specific responses. The anti-IgE antibody (omalizumab) is currently used to treat allergic asthma and chronic idiopathic urticaria, demonstrating the feasibility of inhibiting the IgE:Fc?RI interaction for therapeutic benefit. We have developed multiple approaches to identifying small molecule ligands for the IgE and identified promising leads for further studies. In this proposal, we will further investigate these leads to explore the possibility of producing novel probes for IgE function and inhibition. !